Abstract
The biological basis for the therapeutic mechanisms of depression is still unknown. We have previously performed expressed-sequence tag (EST) analysis to identify some molecular machinery responsible for antidepressant effect. Then, we developed our original cDNA microarray, on which cDNA fragments identified as antidepressant-related genes/ESTs were spotted. In this study, with this microarray followed by Western blot analysis, we have demonstrated the induction of vesicle-associated membrane protein 2(VAMP2/synaptobrevin-2) in rat frontal cortex not only after chronic antidepressant treatment, but also after repeated electroconvulsive treatment. On the other hand, expression of SNAP-25 and syntaxin-1 was not changed by these treatments. These components make a soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor complex with VAMP2 and mediate the synaptic vesicle docking/fusion machinery. In conclusion, it is suggested that VAMP2/synaptobrevin-2 plays important roles in the antidepressant effects. Our results may contribute to a novel model for the therapeutic mechanism of depression and new molecular targets for the development of therapeutic agents.
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Acknowledgements
Sertraline was kindly supplied by Pfizer Pharmaceuticals Inc., NY, USA. M Yamada was supported by a fellowship from the Japan Foundation for Aging and Health. M Tsunoda was supported by a fellowship from the Japan Health Sciences Foundation. This work was in part supported by Health Science Research Grants from Ministry of Health, Labour and Welfare, Ministry of Education, Culture, Sport, Science, and Technology, and Japan Society for the Promotion of Science
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Yamada, M., Takahashi, K., Tsunoda, M. et al. Differential expression of VAMP2/synaptobrevin-2 after antidepressant and electroconvulsive treatment in rat frontal cortex. Pharmacogenomics J 2, 377–382 (2002). https://doi.org/10.1038/sj.tpj.6500135
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DOI: https://doi.org/10.1038/sj.tpj.6500135
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